Pejić was scouted as a model just before her 17th birthday while working at McDonald's,[11] though she has also said in an interview that she was scouted at a swimming pool while still in high school in Melbourne.[12]

Pejić was initially notable for modelling both masculine and feminine clothing. In the Paris fashion shows of January 2011, Pejić walked both the men's and women's shows for Jean-Paul Gaultier and the men's shows for Marc Jacobs. In May 2011, her magazine cover for the New York-based magazine Dossier Journal—in which Pejić is pictured taking off a white shirt with long blond locks in curlers—was ruled too risqué by US bookstores Barnes & Noble and Borders, which covered the image with an opaque sleeve.[13] Concerns were expressed that customers would read Pejić, who at the time was presenting as gender fluid, as a topless woman.[14]

At the Stylenite in July 2011, Pejić appeared on the catwalk both in masculine and feminine clothes from Michalsky.[15] The following year, she modeled bridal creations by Spanish designer Rosa Clara at Barcelona's Bridal Week 2013.[16]

Pejić ranked number 18 on Models.com's Top 50 Models list in 2011,[3][3] was named one of Out's Most Compelling People,[3] and was ranked number 98 in FHM magazine's 100 Sexiest Women in the World 2011,[17] an award that was criticised for its hostile tone to transgender individuals, especially transgender women; the magazine referred to Pejić as a "thing", commenting, "Pass the sick bucket."[18]FHM subsequently removed the copy accompanying Pejić's entry and posted an apology.[19]

Pejić became the first openly transgender model profiled by Vogue, in its May 2015 issue, and also became the first-ever trans woman to sign a cosmetics contract. In 2016, Pejić was awarded "Best International Female Model" by GQ Portugal and the following year she made history by becoming the first transgender woman to appear on the cover of GQ.[24][25][26] Pejić made her major film debut in the 2018 crime thriller film The Girl in the Spider's Web.[27]

In late 2013, Pejić underwent sex reassignment surgery. In September 2014, Pejić announced plans on the Kickstarter crowdfunding platform to create a film about her reassignment surgery and life as a transgender woman. Pejić started off with a projected goal of $40,000, ultimately exceeding the target funding goal.[28][29]